Vascular Endothelial Growth Factor in Ocular Neovascularization and Proliferative Diabetic Retinopathy

Miller, Joan W.; Adamis, Anthony P.; Aiello, Lloyd Paul

doi:10.1002/(sici)1099-0895(199703)13:1<37::aid-dmr174>3.0.co;2-k

Cited by 319 publications

(222 citation statements)

References 7 publications

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“…These include the retinal pigmented epithelium (RPE) (Miller et al, 1997), astrocytes (Stone et al, 1995), Müller cells (Robbins et al, 1997), vascular endothelium (Aiello et al, 1995) and ganglion cells (Ida et al, 2003). These cells differ widely in their responses to hypoxia; in vitro studies show that Müller cells and astrocytes generally produce the greatest amounts of VEGF under hypoxic conditions (Morrison et al, 2007;Aiello et al, 1995;Hata et al, 1995).…”

Section: Retinal Expression Of Vegf and Vegfrmentioning

confidence: 99%

“…However, studies of clinical specimens and various experimental models strongly support the concept that the elevation of blood and tissue glucose levels stimulates the production of angiogenic factors. While many growth factors and cytokines have been implicated in retinal disease, VEGF has been identified as a primary mediator of the vascular alterations in diabetic retinopathy (for review, see Duh and Aiello, 1999;Frank, 2004;Miller et al, 1997). High glucose, oxidative stress, hypoxia and inflammatory reactions, all of which occur in diabetes, have been shown to induce increased expression of VEGF.…”

Section: Clinical Features Of Diabetic Retinopathymentioning

confidence: 99%

“…Overexpression has profound pathological consequences in a variety of disease conditions, including diabetic retinopathy (Duh and Aiello, 1999;Miller et al, 1997). Thus, the biological activity of VEGF is tightly linked to its expression level.…”

Section: Regulation Of Vegf Gene Expression In Diabetic Retinopathymentioning

confidence: 99%

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Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

615

527

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Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

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Section: Retinal Expression Of Vegf and Vegfrmentioning

confidence: 99%

Section: Clinical Features Of Diabetic Retinopathymentioning

confidence: 99%

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Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

615

527

View full text Add to dashboard Cite

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…”

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confidence: 99%

“…Neovascularization plays a role in determining the severity of diabetic retinopathy (DR) due to the effects of several angiogenic and growth factors, including vascular endothelial growth factor (VEGF), plateletderived growth factor (PDGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF-1) [1].…”

mentioning

confidence: 99%

Taq I polymorphism of the vitamin D receptor and risk of severe diabetic retinopathy

et al. 2002

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Neovascularization plays a role in determining the severity of diabetic retinopathy (DR) due to the effects of several angiogenic and growth factors, including vascular endothelial growth factor (VEGF), plateletderived growth factor (PDGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF-1) [1].Chronic hyperglycaemia induces non-severe diabetic retinopathy (DR) in most patients of long duration, but not severe DR in the majority of them, sug- Abstract Aims/hypothesis. Vitamin D, a molecule with antiproliferative, antiangiogenic, antioxidant and immunosuppressive effects, could play a role in the pathogenesis of severe diabetic retinopathy. We examined whether Taq I polymorphism of the vitamin D receptor is involved in the development of severe diabetic retinopathy. Methods. 200 unrelated C-peptide-negative French Type I diabetic patients were randomly selected (male:female, 103:97, age 44.4 12.4 years, diabetes duration: 27.7 10.0 years, BMI: 24.3 3.4 kg/m 2 , HbA 1 c : 8.6 1.3 %). The Taq I site was analysed by PCR followed by digestion with Taq I enzyme. Diabetic retinopathy was assessed by retinal angiography and classified as presence (n = 101) or absence (n = 99) of severe (preproliferative or proliferative) diabetic retinopathy. Results. Frequency of wild-type genotype TT was lower in patients with severe diabetic retinopathy (n = 27) when compared with control subjects (n = 42, OR = 0.5, p = 0.028). Allele frequencies were not different between patients (T: n = 112 and t: n = 90) and control subjects (T: n = 128, and t: n = 70, p = 0.075). Global c 2 (df = 2): p = 0.064. In subjects with diabetes duration of more than 25 years, TT was lower in severe diabetic retinopathy (n = 14) than control subjects (n = 18, OR = 0.3, p = 0.01). Allele frequencies were different between patients (T: n = 68 and t: n = 66) and control subjects (T: n = 52, OR = 0.5, and t: n = 26, OR = 1.9, p = 0.034). Global c 2 (df = 2): p = 0.024. In subjects with HbA 1 c over 9 %, Tt was higher in patients (n = 28) than control subjects (n = 15, OR = 3.1, p = 0.019). Allele frequencies were not different between patients (T: n = 52 and t: n = 38) and control subjects (T: n = 57, and t: n = 29, p = 0.31). Global c 2 (df = 2): p = 0.035. Conclusion/interpretation. In French Type I (insulindependent) diabetic patients, we demonstrate an association between TT form (VDR) and low risk for severe diabetic retinopathy, especially in patients with long duration, and between Tt variant and high risk for severe diabetic retinopathy in subjects with poor glycaemic control. [Diabetologia (2002) 45: 436±442]

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Advanced Glycation End Products in Age-related Macular Degeneration

Ishibashi¹

1998

Arch Ophthalmol

171

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To investigate the localization of N ⑀-(carboxymethyl)lysine (CML), a component and major immunologic epitope of advanced glycation end products, in aged eyes and choroidal neovascular membranes (CNVMs) surgically excised from eyes with agerelated macular degeneration. Methods: Immunohistochemistry for CML was performed using 8 snap-frozen, surgically excised CNVMs. Twelve eyes from patients aged 69 to 82 years and 2 donor eyes, 1 each from a 23-week-old fetus and 21-yearold patient, without age-related macular degeneration or diabetic retinopathy were also examined. To determine if retinal pigment epithelial cells in CNVMs accumulate advanced glycation end products, cytokeratin and CML were stained in paired serial sections. Results: Soft, macular drusen and/or basal laminar and basal linear deposits were observed in 8 of 12 aged eyes. Each case showed CML accumulation, while overlying retinal pigment epithelial cells showed no accumulation in all 12 eyes. In CNVMs, however, retinal pigment epithelial cells showed CML accumulation in their cytoplasm. Conclusion: The additional accumulation of advanced glycation end products in soft, macular drusen and/or retinal pigment epithelial cells may play a role in the pathogenesis of CNVM formation in age-related macular degeneration. Clinical Relevance: Recently, advanced glycation end products have been found to play a role both in aging changes and neovascularization. Localization of advanced glycation end products in the above-mentioned tissue may lead to a better understanding of the pathogenesis of age-related macular degeneration.

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Vascular Endothelial Growth Factor in Ocular Neovascularization and Proliferative Diabetic Retinopathy

Cited by 319 publications

References 7 publications

Vascular endothelial growth factor in eye disease

Vascular endothelial growth factor in eye disease

Taq I polymorphism of the vitamin D receptor and risk of severe diabetic retinopathy

Advanced Glycation End Products in Age-related Macular Degeneration

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